Abstract
This review systematically outlines recent advances in long-acting microneedle-based transdermal drug delivery systems. It begins by introducing the fundamental principles of microneedles (MNs) as a minimally invasive technology and categorizes them by delivery mechanism into solid, coated, dissolving, hollow, hydrogel-forming, and biodegradable types. The review then discusses the design strategies and material platforms engineered for sustained drug release. A key focus is on biodegradable synthetic polymers, such as polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL), and natural polymers like silk fibroin (SF) and chitosan (CS), which enable prolonged drug release through their tunable degradation rates. Furthermore, it describes the incorporation of advanced drug carriers, including liposomes and polymeric nanoparticles/microparticles, into MNs to further extend release duration and enhance drug-loading capacity. Finally, the major challenges for clinical translation are addressed, including ensuring batch-to-batch consistency in manufacturing, maintaining sterility, and the necessity for more comprehensive validation of long-term in vivo efficacy and safety.